Nanosecond pulsed electric field (NsPEF) ablation effectively eliminates early-stage hepatocellular carcinoma (HCC) by local ablation and advanced HCC by inducing a remarkable and sustained host immune response. However, this approach is not sufficient to prevent cancer progression, and complementary approaches are necessary for effective immunotherapy. In this study, we evaluated the immunoactivating effects and mechanisms of action of nsPEF ablation and PD-1 blockade on an HCC orthotopic xenograft mouse model. Briefly, 24 C57BL-6J tumor-bearing mice were randomly assigned to three groups: nsPEF ablation group, anti-PD-1 administration group, and untreated control group. Tumor-infiltrating T, B, and NK cell levels and plasma concentrations of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-5, IL-6, and IL-10), Th9 (IL-9), and Th17 (IL-17A, IL-17F, IL-21, and IL-22) cytokines were evaluated. Both nsPEF ablation and anti-PD-1 treatment induced immune cell infiltration in local tumors and modulated cytokine levels in the peripheral blood, with distinct changes in the two treatment groups. Based on these findings, both nsPEF ablation and PD-1 antibody administration can trigger a local and systemic immune response in a partially complementary manner, and nsPEF ablation should be considered along with PD-1 blockade for the treatment of HCC.

中文翻译：

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纳秒脉冲电场免疫激活和 PD-1 阻断在鼠肝细胞癌中的比较分析。

纳秒脉冲电场 (NsPEF) 消融通过局部消融有效消除早期肝细胞癌 (HCC)，并通过诱导显着且持续的宿主免疫反应消除晚期肝细胞癌。然而，这种方法不足以阻止癌症进展，有效的免疫治疗需要补充方法。在本研究中，我们评估了 nsPEF 消融和 PD-1 阻断对 HCC 原位异种移植小鼠模型的免疫激活作用和作用机制。简而言之，将 24 只 C57BL-6J 荷瘤小鼠随机分为三组：nsPEF 消融组、抗 PD-1 给药组和未治疗对照组。肿瘤浸润性 T、B 和 NK 细胞水平以及 Th1（IL-2、IFN- γ和 TNF - α）的血浆浓度)、Th2（IL-4、IL-5、IL-6 和 IL-10）、Th9（IL-9）和 Th17（IL-17A、IL-17F、IL-21 和 IL-22）细胞因子被评估。nsPEF 消融和抗 PD-1 治疗均诱导局部肿瘤中的免疫细胞浸润并调节外周血中的细胞因子水平，两个治疗组的变化明显。基于这些发现，nsPEF 消融和 PD-1 抗体给药均可以部分互补的方式触发局部和全身免疫反应，应考虑将 nsPEF 消融与 PD-1 阻断剂一起用于治疗 HCC。